Alternative medicine by definition is medicine that has not been shown to work any better than placebo. Patients think they are helped by alternative medicine. Placebos, by definition, do “please” patients. We would all like to please our patients, but we don’t want to lie to them. Is there a compromise? Is there a way we can ethically elicit the same placebo response that alternative theorists elicit by telling their patients fairy tales about qi, subluxations, or the memory of water?

Psychiatrist Morgan Levy has written a book entitled Placebo Medicine. It’s available free online. In it, he makes an intriguing case for incorporating the best alternative medicine placebo treatments into mainstream medicine.

In a light, entertaining style, he covers the placebo effect, suggestibility, and the foibles of the human thought processes that allow us to believe a treatment works when it doesn’t.

“Thinking like a human” is not a logical way to think but it is not a stupid way to think either. You could say that our thinking is intelligently illogical. Millions of years of evolution did not result in humans that think like a computer. It is precisely because we think in an intelligently illogical way that our predecessors were able to survive… [by acting on quick assumptions rather than waiting for comprehensive, definitive data]… We have evolved to survive, not to play chess.

He offers evidence from scientific studies indicating that belief in a treatment and the power of suggestion can have actual physiologic consequences such as production of endorphins or changes on brain imaging studies. He spices his narrative with colorful stories, including anecdotes from his own sex life and an impassioned plea (tongue in cheek?) for everyone to drink coffee for its proven benefits. (more…)

In case you’re coming late to this discussion (or have ADD), I’ve summarized Dr. Kimball Atwood’s terrific analysis of the ongoing clinical trial (TACT trial) in which convicted felons were awarded $30 million by the NIH.

***

In one of the most unethical clinical trial debacles of our time, the NIH approved a research study (called the TACT Trial – Trial to Assess Chelation Therapy – a supposed treatment for arteriosclerosis) in which the treatment had no evidence for potential benefit, and clear evidence of potential harm – and even the risk of death. Amazingly, the researchers neglected to mention this risk in their informed consent document. The NIH awarded $30 million of our tax dollars to ~100 researchers to enroll 2000 patients in this risky study (ongoing from 2003-present). Even more astounding is the fact that several of the researchers have been disciplined for substandard practices by state medical boards; several have been involved in insurance fraud; at least 3 are convicted felons.

But wait, there’s more.

The treatment under investigation, IV injection of Na2EDTA, is specifically contraindicated for “generalized arteriosclerosis” by the FDA. There have been over 30 reported cases of accidental death caused by the administration of this drug – and prior to the TACT, 4 RCTs and several substudies of chelation for either CAD or PVD, involving 285 subjects, had been reported.None found chelation superior to placebo.

So, Why Was This Study Approved?

The NIH and the TACT principal investigator (PI) argued that there was a substantial demand for chelation, creating a “public health imperative” to perform a large trial as soon as possible. In reality, the number of people using the therapy was only a small fraction of what the PI reported.

It’s hard to know exactly what happened “behind the scenes” to pressure NIH to go forward with the study – however a few things are clear: 1) the National Heart, Lung, and Blood Institute (NHLBI) initially declined to approve the study based on lack of scientific merit 2) congressman Dan Burton and at least one of his staffers (Beth Clay) and a lobbyist (Bill Chatfield) worked tirelessly to get the study approved through a different institute – NCCAM 3) some of the evidence used to support the trial was falsified (The RFA cited several articles by Edward McDonagh, the chelationist who had previously admitted in a court of law to having falsified his data.) 4) The NIH Special Emphasis Panel that approved the TACT protocol included L. Terry Chappell, whom the protocol had named as a participant in the TACT.

All evidence seems to suggest that political meddling managed to trump science in this case – putting the lives of 2000 study subjects at risk, without any likely benefit to them or medicine.

A formal analysis of the sordid history and ethical violations of the TACT trial was published by the Medscape Journal of Medicine on May 13, 2008. Atwood et al. provide a rigorous, 9-part commentary with 326 references in review of the case. Congressman Burton’s staffer, Beth Clay, published what is essentially a character assassination of Dr. Atwood in response.

The NIH Writes TACT Investigators a Strongly Worded Letter

On May 27, 2009 the Office for Human Research Protections Committee sent a letter to the investigators of TACT, stating that they found, “multiple instances of substandard practices, insurance fraud, and felony activity on the part of the investigators.” The letter describes a list of irregularities and recommends various changes to the research protocol.

It is almost unheard of for a letter from the NIH to state that research study investigators are guilty of fraud and felony activity – but what I don’t understand is why they haven’t shut down the study. Perhaps this is their first step towards that goal? Let’s hope so.

Conclusion

The TACT trial has subjected 2000 unwary subjects and $30 million of public money to an unethical trial of a dubious treatment that, had it been accurately represented and judged by the usual criteria, would certainly have been disqualified. Political meddling in health and medical affairs is dangerous business, and must be opposed as strongly as possible. Congressmen like Tom Harkin and Dan Burton should not be allowed to push their political agendas and requests for publicly funded pseudoscience on the NIH. I can only hope that the new NIH director will have the courage to fend off demands for unethical trials from political appointees.

We’ve written a lot about anti-vaccine zealotry on this blog, as Steve and I take a particular interest in this particular form of dangerous pseudoscience for a number of reasons. One reason, of course, is that the activities of antivaccine groups like Generation Rescue and its spokesmodel since 2007 (Jenny McCarthy, a frequent topic on this blog) have started to frighten parents about vaccines enough that vaccination rates are falling well below that required for herd immunity in some parts of the country. Indeed, McCarthy, at the behest of her handlers in Generation Rescue, serves up a regular “toxic” brew of misinformation and nonsense about vaccines, most recently in a video that was the subject of a post by Val Jones about her unbelievably pseudoscience-laden blather. Truly, it has to be seen to be believed. Meanwhile, Generation Rescue has sent McCarthy on a media propaganda tour for her latest antivaccine pro-quackery book and set up a misinformation-laden propaganda site called Fourteen Studies (blogged about by Steve Novella, Mark Crislip, and, of course, yours truly) in which they attack well-designed studies that have failed to confirm their pet idea that somehow, some way, vaccines must be the cause of autism. And, when their pseudoscience is criticized, the antivaccine movement has a tendency to launch vicious ad hominem attacks, as they recently did against Steve Novella and have done multiple times in the past against me.

However, there is one other consequence of the antivaccine movement, however, and it is at least as important as the public health implications of the potential dimunition of herd immunity caused by the fear mongering of groups like Generation Rescue. That consequence is the cottage industry of “biomedical” treatments to which desperate parents subject their children. Gluten-free diets, chelation therapy (which has caused deaths), hyperbaric oxygen chambers (a recent story described a child getting severely burned when one of these caught fire), autistic children have been subjected to it all. But of all the biomedical woo to which autistic children have been subjected, one form of woo stands out as being particularly heinous. Indeed, I agree with our fearless leader Steve in characterizing it as an “atrocity.”

I’m referring to Mark and David Geier’s favored “treatment” for autistic children, namely a drug called Lupron.(more…)

I’ve written before about clinical trials as one place where “the rubber hits the road,” so to speak regarding the interface between science-based medicine and actual medical practice. Another critical place where an equal amount of rubber hits an equal amount of road is how the medical system and the law deal with the medical care of minors. In the vast majority of cases, parents take their children to physicians ostensibly practicing science-based medicine and, more or less, follow their advice. One of the more common areas where there is resistance to science-based medicine is, of course, the issue of vaccination, which I and other bloggers at SBM have written about extensively. Another issue, which has not yet been touched upon on this blog, is what to do about parents who refuse chemotherapy for their children with curable childhood cancers or children who refuse chemotherapy whose parents either agree with them or are unwilling to do the hard work of convincing their children that they must undergo therapy. Most often, the reason cited by such “chemotherapy refuseniks” is either religion or a desire to undergo “alternative” therapy rather than conventional therapy. One such case, a particularly high profile one, has been in the news over the last couple of weeks. In this post, I plan to discuss the case of Daniel Hauser, a 13-year-old boy from Minnesota with Hodgkin’s lymphoma who, after one round of chemotherapy, is currently refusing further therapy. This case ended up in court (as these cases often do) and led to a decision that is likely to satisfy no one (as these cases nearly always do).

Before I discuss Daniel’s case in more depth, however, let me make one thing clear. From my perspective, competent adults have the right to choose whatever treatment they wish–or to refuse treatment altogether–for virtually any condition. The sole exception that I can think of would be the case of a highly contagious infectious disease, where society has a right to prevent epidemics and, if necessary, quarantine someone who refuses treatment and refuses to avoid interaction with others. Note, however, that the right competent adults to choose whatever quackery they desire should in no way be construed to imply that quacks have any sort of “right” to provide them with quack treatments. The reason is that providing such treatments inherently involves making claims for them that are not supportable by science. In essence, selling such treatments involves fraud, even if the practitioner is a true believer and just as deluded about the efficacy of the woo he is selling as the person buying it is. Be that as it may, if a competent adult wants to refuse treatment and understands the consequences, then I will call him a fool if what he has is a potentially very curable disease like Hodgkin’s disease and chooses bogus (word choice intentional) alternative “cures” instead, but it’s his call.

However, from my perspective (and that of the law in most states) the key to such self-determination is that the person must be informed of and understand the consequences of his actions, and there are three components to this understanding. First, of course, is mental competence; i.e., no serious untreated mental illness that impairs a person’s ability to perceive reality can be present. Untreated schizophrenia, for example, can definitely interfere with a person’s ability to evaluate information. The second is the ability to understand the disease and what the consequences of treatment or doing nothing are. That is why adults with mental retardation severe enough to prevent them from understanding are in general not considered competent to make such decisions. Indeed, it is why parents are expected to act on the behalf of their normal children to make such decisions. Finally, there is informed consent. A person refusing treatment must be told the consequences of his refusal and acknowledge them. Whether he believes what he is told is another matter, but it is not up to physicians to force treatment on someone just because that person doesn’t believe what they tell him, as long as the first two conditions are met.

The conflict arises when a parent decides to pursue quackery for a life-threatening but potentially curable illness for a child or a child refuses therapy. It is on such occasions that society as represented by the state has a compelling interest in overriding the parent’s decision and making sure that the child gets the best science-based treatment available. It is also a situation when parental rights, rights of self-determination, and the legitimate interest of society in protecting children can all clash in a most chaotic and nasty manner. That is exactly what is at issue in the case of Daniel Hauser, as described in a news report of the testimony given in his case:(more…)

If there’s one thing I’ve learned in my years promoting skepticism and science in medicine and writing critically about various forms of unscientific medical practices and outright quackery, it’s that there will always be pushback. Much, if not most, of the time, it’s just insults online. However, occasionally, the pushback enters into the realm of real life. I can remember the very first time this happened to me. It was in 2005, and a man by the name of William P. O’Neill of the Canadian Cancer Research Group sent legal threats to my Department Chairman, my Division Chief, and my Cancer Center Director. The legal threat was clearly vacuous, as Mr. O’Neill seemed upset mainly that I had praised his arch-nemesis, Australian skeptic Peter Bowditch (who even keeps a running tally of threats he receives from Mr. O’Neill under the heading The GAL Chronicles, where GAL stands for “gutless anonymous liar”). I must admit, at the time it scared the crap out of me, but the reaction of my Chairman at the time, Dr. Stephen Lowry, was classic in that he said he did not care what I did in my spare time and referred to Mr. O’Neill as a “cowardly bully.” From then on, every time Mr. O’Neill tried something similar, I simply replied that I was forwarding his e-mail to Dr. Lowry (who was amused by all this) and thanked him for his concern.

More recently, J.B. Handley wrote a rather ugly screed (one of two, actually) about me. Somehow, this screed was e-mailed to my cancer center director. Whether Mr. Handley, one of the crew at Age of Autism, or an AoA reader did it, I don’t know. However, it is typical behavior of the anti-vaccine movement. Based on this history, I’ve concluded that, if you’re going to be a skeptic you’d better be prepared for this sort of thing, and if you’re going to blog under a pseudonym you’d better expect that sooner or later someone will try very, very hard indeed to “out” you and use that against you–which is of course blogging at SBM is in a way liberating in that it removes that threat.

However, whatever obnoxiousness or attempts to harass me at my job I may on occasion have to worry about, one thing I don’t have to worry about (much) is legal threats, at least as long as I keep all my ducks in a row, so to speak. In the U.S., libel is a very difficult charge to prove. The First Amendment gives wide latitude to free speech, and that places the burden of proof on the plaintiff to show that a statement is defamatory, with libel being in essence written defamation. In general, this is what constitutes defamation in the U.S.:

In order for the person about whom a statement is made to recover for libel, the false statement must be defamatory, meaning that it actually harms the reputation of the other person, as opposed to being merely insulting or offensive.

The statement(s) alleged to be defamatory must also have been published to at least one other person (other than the subject of the statement) and must be “of and concerning” the plaintiff. That is, those hearing or reading the statement must identify it specifically with the plaintiff.

The statement(s) alleged to be defamatory must also be a false statement of fact. That which is name-calling, hyperbole, or, however characterized, cannot be proven true or false, cannot be the subject of a libel or slander claim.

The defamatory statement must also have been made with fault. The extent of the fault depends primarily on the status of the plaintiff. Public figures, such as government officials, celebrities, well-known individuals, and people involved in specific public controversies, are required to prove actual malice, a legal term which means the defendant knew his statement was false or recklessly disregarded the truth or falsity of his statement. In most jurisdictions, private individuals must show only that the defendant was negligent: that he failed to act with due care in the situation.

A defamation claim — at least one based upon statements about issues that are matters of public interest — will likely fail if any of these elements are not met.

As you can see, it is a high bar of evidence to overcome to prove libel. Of course, that is a two-edged sword in that it allows J.B. Handley to slime me whenever he wishes, with little I can do about it, but I am also allowed, as I see fit, to respond or not to such attacks. I can also continue to criticize anti-vaccine propagandists like Mr. Handley as I see fit. Unfortunately, for my U.K. colleagues, the same is most assuredly not true in British courts, where the rules are very much weighted against the defendant. Witness this travesty of a ruling on the libel case against Simon Singh, coauthor with Edzard Ernst of Trick or Treatment: The Undeniable Facts about Alternative Medicine (which Harriet Hall reviewed last year) by the British Chiropractic Association, as related by Jack of Kent. This ruling came about because the BCA did not like an article that Singh wrote for The Guardian entitled Beware the spinal trap.(more…)

It’s times like these when I’m happy that I haven’t published in too many Elsevier Journals during the course of my career. Actually, I’m not sure if I’ve ever published in an Elsevier journal, although I have reviewed manuscripts for them. In any case, I say that because on Thursday, it was revealed that pharmaceutical company Merck, Sharp & Dohme paid Elsevier to produce a fake medical journal that, to any superficial examination, looked like a real medical journal but was in reality nothing more than advertising for Merck. As reported by The Scientist:

Merck paid an undisclosed sum to Elsevier to produce several volumes of a publication that had the look of a peer-reviewed medical journal, but contained only reprinted or summarized articles–most of which presented data favorable to Merck products–that appeared to act solely as marketing tools with no disclosure of company sponsorship.

“I’ve seen no shortage of creativity emanating from the marketing departments of drug companies,” Peter Lurie, deputy director of the public health research group at the consumer advocacy nonprofit Public Citizen, said, after reviewing two issues of the publication obtained by The Scientist. “But even for someone as jaded as me, this is a new wrinkle.”

The Australasian Journal of Bone and Joint Medicine, which was published by Exerpta Medica, a division of scientific publishing juggernaut Elsevier, is not indexed in the MEDLINE database, and has no website (not even a defunct one). The Scientist obtained two issues of the journal: Volume 2, Issues 1 and 2, both dated 2003. The issues contained little in the way of advertisements apart from ads for Fosamax, a Merck drug for osteoporosis, and Vioxx. (Click here and here to view PDFs of the two issues.)

This is wrong on so many levels that it’s hard to know where to begin.(more…)

Loose Ends: Dr. Koh and More

After Dr. Federman’s letter and my reply, posted in Part V of this series,† there seemed little point in pursuing the matter further. Although Dr. Federman never answered my reply, he did send, at my request, a copy of Commissioner of Public Health Howard Koh‘s written “construction of the events in the Massachusetts Special Commission.” As you may recall, those events had occurred at meetings that Dr. Koh never attended:

July 29, 2002

Dear Dr. Federman:

I have had an opportunity to review Dr. Kimball Atwood’s characterizations of the role Dr. David Eisenberg played as an advisor and designee of the Department of Public Health (DPH) and I am writing to clarify several misrepresentations of that role. As you may know, I personally selected Dr. Eisenberg as my designee for the Massachusetts Special Commission on Complementary and Alternative Medical Practitioners based on his high level of scientific and clinical expertise in the field, as well as his international reputation for evidence-based research. I felt at that time, as I do now, that he was the appropriate choice to represent the Department and I am extremely grateful for his advice and his integrity during this most contentious process.

During the course of the Commission, Dr. Eisenberg brought to my attention some of the conflicts that had arisen among the members, despite his attempts to diffuse the hostility and to engage the members in collegial debate. In an effort to overcome these difficulties and deflect unwarranted criticism, Nancy Ridley, Assistant Commissioner for Health Quality Management, attended the meetings over the last six months as the DPH voting designee, with Dr. Eisenberg as an advisor. She also organized a DPH workgroup of the Commission in an attempt to bring consensus and closure to what had become a very polarized and highly personalized process.

I need to state emphatically that the approval of the final Commission report is my responsibility, and is largely a product of the DPH workgroup that Assistant Commissioner Ridley chaired. Dr. Eisenberg had actually not been supportive of either the “majority” or “minority” reports that were originally presented, and neither was Ms. Ridley. She attempted to address as many of Dr. Eisenberg’s concerns as possible but knew he still had issues with the final document. She feels very strongly that there needs to be regulatory oversight of non-physician practitioners of complementary and alternative naturopathic practice. Assistant Commissioner Ridley, on behalf of the Department and with my consent, signed the report that included a significant number of revisions which narrowed the scope of practice, ensured collaborative relationships between physician and non-physician practitioners, and broadened the scope of any proposed regulatory oversight required. Dr. Eisenberg’s advice to DPH was delivered in a fair and balanced manner based his outstanding experience as a clinician and scientist.

I believe that one of the contributing factors for the polarization within the Commission had little to do with Dr. Eisenberg’s participation rather than that of his staffperson, Michael Cohen, who attended Commission meetings in his absence. Mr. Cohen was repeatedly characterized as the alternate DPH designee, which he was not.

In summary, Dr. Eisenberg’s expertise and professionalism throughout this difficult process have been greatly appreciated by the Department. DPH was truly fortunate to be represented and advised by a person of Dr. Eisenberg’s stature and character. I would be more that pleased to speak to you or Dean Martin on his behalf. Please feel free to contact me at xxx.xxx.xxxx if you need any additional information.

Sincerely,

Howard K. Koh, MD, MPH

The range of self-serving misrepresentations in that letter is wide, and is worrisome in someone who will be “responsible for the major health agencies, including the CDC, FDA and NIH, and [will be] the leading health advisor to the Secretary of HHS.” I have already discussed some of the facts here and here, and will add more now.

Arguably the most difficult aspect of science-based medicine is where the rubber hits the road, so to speak. That’s where scientists and physicians take the results of preclinical studies performed in vitro in biochemical assays and cell culture models and in vivo in animal models to humans. There are numerous reasons for this, not the least of which that preclinical models, contrary to what animal rights activists would like you to believe, do not predict human responses to new therapeutic agents as much as we would like. However, the single biggest reason that we cannot answer questions in human studies as easily as we can in cell culture and animal studies is ethics. Of course, answering questions using cell culture and animal studies is not “easy,” either, but performing studies using human beings as subjects is an order of magnitude (at least) more difficult because the potential to cause harm exists, and if harm is caused by the experimental treatment under study, that harm will be done to human beings, rather than cells in a dish or mice bred for research.

The “gold standard” type of study that we do to test the efficacy of a new drug is known as the randomized, placebo-controlled, double-blinded study, often abbreviated RCT. Indeed, this remains the gold standard and is accorded the highest level of “power” in the framework of evidence-based medicine. Of course, as we have argued time and time again, using the RCT to test therapies that are incredibly implausible on a strictly scientific basis (homeopathy or reiki, for instance) inevitably leads to numerous “false positives” in which the therapy appears to produce results statistically significantly better than the control. John Ioannidis has done numerous clever analyses that demonstrate how easily clinical research is led astray if it is not grounded in scientific plausibility. Indeed, the probability of false positive studies increases, the more improbable the modality. It is for these very reasons that we have proposed the concept of science-based medicine, which takes into account estimates of prior probability based on preclinical studies and basic scientific principles, rather than evidence-based medicine, which does not. Indeed, Wally Sampson has even proposed a “plausibility scale” for rating RCTs, and Steve Novella has pointed out how difficult it can be to interpret the medical literature.(more…)

I have now had time to look into the allegations in your letter of June 14th which, incidentally, I shared with Dr. David Eisenberg and he with several others. I have sought consultation about our exchanges and the gist of my response follows.

Some of your concerns and allegations are very helpful and constructive. Perceptions are particularly important in controversial fields where there is limited objective proof. Your cautions and interpretations in this area have been very useful to us.

Some of what you said is just plain wrong. This includes the allegation the Harvard has “a stake” in the area and therefore would not look into your allegations objectively. Relatedly, Dr. Howard Koh has written us a construction of the events in the Massachusetts Special Commission that is strikingly different from yours. And Dr. Anthony Komoroff has pointed out that many of your comments about the InteliHealth treatment of CAM are now grossly out of date as the material inherited from another provider has been reviewed by HMS faculty and modified. [Indeed, you have referred in other correspondence to modifications you have noticed.] Dr. Komaroff also commented on the misleading way your citation the treatment of homeopathy was disconnected from the rest of the paragraph.

Some of what you said is a matter of taste or interpretation, where even well intentioned people may disagree. In this particular area I have weighed your arguments carefully and, in places, learned from them.

But I think the biggest difference may be in a misperception about what our purposes are. The Council of Academic Deans of Harvard Medical School approved beginning a Division of Research and Education in Complementary and Alternative Therapies with exactly the focus described. Our goal is to do peer-reviewed basic and clinical research on the claimed, but unproven, efficacies of complementary and alternative approaches to therapeutics. The recent scientific sessions and requests for proposal held by the Division are clear testament to this intent. In addition, in common with the Association of American Medical Colleges and most of the allopathic schools of medicine, we intend to teach our students something about CAM and in particular how to assess its claims rigorously. We do not, repeat NOT, have any intention of making our students CAM practitioners. They have enough to do learning what we have always focused on.

I only recently began contributing to SBM, bringing not any particular expertise or scholarship but rather the perspective of a student. My goal in blogging is not to focus on issues specific to my school, of which I am quite fond and proud in general. Instead I hope to use my experiences, which SBM editors and readers tell me are not unique, to illustrate how CAM can interact with medical education. When writing, I constantly remind myself, “Everything you know about homeopathy and naturopathy was heavily influenced by the SBM docs, so try not to parrot their arguments lest you look like a brainwashed fanboy. Focus on relaying your experiences and trust readers to reach their own conclusions.” As a result, some have called my critiques a bit mild, but I can accept blandness to avoid seeming arrogant beyond my qualifications.

I was surprised, therefore, to be told by leaders of a campus CAM group that my most recent SBM post was full of personal attacks. (more…)